Assessment of the occurrence of nanoparticles in Swiss industry and evaluation of the appropriatenesss of the measurement devices to determine the workforce exposure

Abstract : The occupational health risk involved with handling nanoparticles is the probability that a worker will experience an adverse health effect: this is calculated as a function of the worker's exposure relative to the potential biological hazard of the material. Addressing the risks of nanoparticles requires therefore knowledge on occupational exposure and the release of nanoparticles into the environment as well as toxicological data. However, information on exposure is currently not systematically collected; therefore this risk assessment lacks quantitative data. This thesis aimed at, first creating the fundamental data necessary for a quantitative assessment and, second, evaluating methods to measure the occupational nanoparticle exposure. The first goal was to determine what is being used where in Swiss industries. This was followed by an evaluation of the adequacy of existing measurement methods to assess workplace nanopaiticle exposure to complex size distributions and concentration gradients. The study was conceived as a series of methodological evaluations aimed at better understanding nanoparticle measurement devices and methods. lt focused on inhalation exposure to airborne particles, as respiration is considered to be the most important entrance pathway for nanoparticles in the body in terms of risk. The targeted survey (pilot study) was conducted as a feasibility study for a later nationwide survey on the handling of nanoparticles and the applications of specific protection means in industry. The study consisted of targeted phone interviews with health and safety officers of Swiss companies that were believed to use or produce nanoparticles. This was followed by a representative survey on the level of nanoparticle usage in Switzerland. lt was designed based on the results of the pilot study. The study was conducted among a representative selection of clients of the Swiss National Accident Insurance Fund (SUVA), covering about 85% of Swiss production companies. The third part of this thesis focused on the methods to measure nanoparticles. Several pre- studies were conducted studying the limits of commonly used measurement devices in the presence of nanoparticle agglomerates, This focus was chosen, because several discussions with users and producers of the measurement devices raised questions about their accuracy measuring nanoparticle agglomerates and because, at the same time, the two survey studies revealed that such powders are frequently used in industry. The first preparatory experiment focused on the accuracy of the scanning mobility particle sizer (SMPS), which showed an improbable size distribution when measuring powders of nanoparticle agglomerates. Furthermore, the thesis includes a series of smaller experiments that took a closer look at problems encountered with other measurement devices in the presence of nanoparticle agglomerates: condensation particle counters (CPC), portable aerosol spectrometer (PAS) a device to estimate the aerodynamic diameter, as well as diffusion size classifiers. Some initial feasibility tests for the efficiency of filter based sampling and subsequent counting of carbon nanotubes (CNT) were conducted last. The pilot study provided a detailed picture of the types and amounts of nanoparticles used and the knowledge of the health and safety experts in the companies. Considerable maximal quantities (> l'000 kg/year per company) of Ag, Al-Ox, Fe-Ox, SiO2, TiO2, and ZnO (mainly first generation particles) were declared by the contacted Swiss companies, The median quantity of handled nanoparticles, however, was 100 kg/year. The representative survey was conducted by contacting by post mail a representative selection of l '626 SUVA-clients (Swiss Accident Insurance Fund). It allowed estimation of the number of companies and workers dealing with nanoparticles in Switzerland. The extrapolation from the surveyed companies to all companies of the Swiss production sector suggested that l'309 workers (95%-confidence interval l'073 to l'545) of the Swiss production sector are potentially exposed to nanoparticles in 586 companies (145 to l'027). These numbers correspond to 0.08% (0.06% to 0.09%) of all workers and to 0.6% (0.2% to 1.1%) of companies in the Swiss production sector. To measure airborne concentrations of sub micrometre-sized particles, a few well known methods exist. However, it was unclear how well the different instruments perform in the presence of the often quite large agglomerates of nanostructured materials. The evaluation of devices and methods focused on nanoparticle agglomerate powders. lt allowed the identification of the following potential sources of inaccurate measurements at workplaces with considerable high concentrations of airborne agglomerates: - A standard SMPS showed bi-modal particle size distributions when measuring large nanoparticle agglomerates. - Differences in the range of a factor of a thousand were shown between diffusion size classifiers and CPC/SMPS. - The comparison between CPC/SMPS and portable aerosol Spectrometer (PAS) was much better, but depending on the concentration, size or type of the powders measured, the differences were still of a high order of magnitude - Specific difficulties and uncertainties in the assessment of workplaces were identified: the background particles can interact with particles created by a process, which make the handling of background concentration difficult. - Electric motors produce high numbers of nanoparticles and confound the measurement of the process-related exposure. Conclusion: The surveys showed that nanoparticles applications exist in many industrial sectors in Switzerland and that some companies already use high quantities of them. The representative survey demonstrated a low prevalence of nanoparticle usage in most branches of the Swiss industry and led to the conclusion that the introduction of applications using nanoparticles (especially outside industrial chemistry) is only beginning. Even though the number of potentially exposed workers was reportedly rather small, it nevertheless underscores the need for exposure assessments. Understanding exposure and how to measure it correctly is very important because the potential health effects of nanornaterials are not yet fully understood. The evaluation showed that many devices and methods of measuring nanoparticles need to be validated for nanoparticles agglomerates before large exposure assessment studies can begin. Zusammenfassung : Das Gesundheitsrisiko von Nanopartikel am Arbeitsplatz ist die Wahrscheinlichkeit dass ein Arbeitnehmer einen möglichen Gesundheitsschaden erleidet wenn er diesem Stoff ausgesetzt ist: sie wird gewöhnlich als Produkt von Schaden mal Exposition gerechnet. Für eine gründliche Abklärung möglicher Risiken von Nanomaterialien müssen also auf der einen Seite Informationen über die Freisetzung von solchen Materialien in die Umwelt vorhanden sein und auf der anderen Seite solche über die Exposition von Arbeitnehmenden. Viele dieser Informationen werden heute noch nicht systematisch gesarnmelt und felilen daher für Risikoanalysen, Die Doktorarbeit hatte als Ziel, die Grundlagen zu schaffen für eine quantitative Schatzung der Exposition gegenüber Nanopartikel am Arbeitsplatz und die Methoden zu evaluieren die zur Messung einer solchen Exposition nötig sind. Die Studie sollte untersuchen, in welchem Ausmass Nanopartikel bereits in der Schweizer Industrie eingesetzt werden, wie viele Arbeitnehrner damit potentiel] in Kontakt komrrien ob die Messtechnologie für die nötigen Arbeitsplatzbelastungsmessungen bereits genügt, Die Studie folcussierte dabei auf Exposition gegenüber luftgetragenen Partikel, weil die Atmung als Haupteintrittspforte iïlr Partikel in den Körper angesehen wird. Die Doktorarbeit besteht baut auf drei Phasen auf eine qualitative Umfrage (Pilotstudie), eine repräsentative, schweizerische Umfrage und mehrere technische Stndien welche dem spezitischen Verständnis der Mëglichkeiten und Grenzen einzelner Messgeräte und - teclmikeri dienen. Die qualitative Telephonumfrage wurde durchgeführt als Vorstudie zu einer nationalen und repräsentativen Umfrage in der Schweizer Industrie. Sie zielte auf Informationen ab zum Vorkommen von Nanopartikeln, und den angewendeten Schutzmassnahmen. Die Studie bestand aus gezielten Telefoninterviews mit Arbeit- und Gesundheitsfachpersonen von Schweizer Unternehmen. Die Untemehmen wurden aufgrund von offentlich zugànglichen lnformationen ausgewählt die darauf hinwiesen, dass sie mit Nanopartikeln umgehen. Der zweite Teil der Dolctorarbeit war die repräsentative Studie zur Evalniernng der Verbreitnng von Nanopaitikelanwendungen in der Schweizer lndustrie. Die Studie baute auf lnformationen der Pilotstudie auf und wurde mit einer repräsentativen Selektion von Firmen der Schweizerischen Unfall Versicherungsanstalt (SUVA) durchgeüihxt. Die Mehrheit der Schweizerischen Unternehmen im lndustrieselctor wurde damit abgedeckt. Der dritte Teil der Doktorarbeit fokussierte auf die Methodik zur Messung von Nanopartikeln. Mehrere Vorstudien wurden dnrchgefîihrt, um die Grenzen von oft eingesetzten Nanopartikelmessgeräten auszuloten, wenn sie grösseren Mengen von Nanopartikel Agglomeraten ausgesetzt messen sollen. Dieser F okns wurde ans zwei Gründen gewählt: weil mehrere Dislcussionen rnit Anwendem und auch dem Produzent der Messgeràte dort eine Schwachstelle vermuten liessen, welche Zweifel an der Genauigkeit der Messgeräte aufkommen liessen und weil in den zwei Umfragestudien ein häufiges Vorkommen von solchen Nanopartikel-Agglomeraten aufgezeigt wurde. i Als erstes widmete sich eine Vorstndie der Genauigkeit des Scanning Mobility Particle Sizer (SMPS). Dieses Messgerät zeigte in Präsenz von Nanopartikel Agglorneraten unsinnige bimodale Partikelgrössenverteilung an. Eine Serie von kurzen Experimenten folgte, welche sich auf andere Messgeräte und deren Probleme beim Messen von Nanopartikel-Agglomeraten konzentrierten. Der Condensation Particle Counter (CPC), der portable aerosol spectrometer (PAS), ein Gerät zur Schàtzung des aerodynamischen Durchniessers von Teilchen, sowie der Diffusion Size Classifier wurden getestet. Einige erste Machbarkeitstests zur Ermittlnng der Effizienz von tilterbasierter Messung von luftgetragenen Carbon Nanotubes (CNT) wnrden als letztes durchgeiührt. Die Pilotstudie hat ein detailliiertes Bild der Typen und Mengen von genutzten Nanopartikel in Schweizer Unternehmen geliefert, und hat den Stand des Wissens der interviewten Gesundheitsschntz und Sicherheitsfachleute aufgezeigt. Folgende Typen von Nanopaitikeln wurden von den kontaktierten Firmen als Maximalmengen angegeben (> 1'000 kg pro Jahr / Unternehrnen): Ag, Al-Ox, Fe-Ox, SiO2, TiO2, und ZnO (hauptsächlich Nanopartikel der ersten Generation). Die Quantitäten von eingesetzten Nanopartikeln waren stark verschieden mit einem ein Median von 100 kg pro Jahr. ln der quantitativen Fragebogenstudie wurden l'626 Unternehmen brieflich kontaktiert; allesamt Klienten der Schweizerischen Unfallversicherringsanstalt (SUVA). Die Resultate der Umfrage erlaubten eine Abschätzung der Anzahl von Unternehmen und Arbeiter, welche Nanopartikel in der Schweiz anwenden. Die Hochrechnung auf den Schweizer lndnstriesektor hat folgendes Bild ergeben: ln 586 Unternehmen (95% Vertrauensintervallz 145 bis 1'027 Unternehmen) sind 1'309 Arbeiter potentiell gegenüber Nanopartikel exponiert (95%-Vl: l'073 bis l'545). Diese Zahlen stehen für 0.6% der Schweizer Unternehmen (95%-Vl: 0.2% bis 1.1%) und 0.08% der Arbeiternehmerschaft (95%-V1: 0.06% bis 0.09%). Es gibt einige gut etablierte Technologien um die Luftkonzentration von Submikrometerpartikel zu messen. Es besteht jedoch Zweifel daran, inwiefern sich diese Technologien auch für die Messurrg von künstlich hergestellten Nanopartikeln verwenden lassen. Aus diesem Grund folcussierten die vorbereitenden Studien für die Arbeitsplatzbeurteilnngen auf die Messung von Pulverri, welche Nan0partike1-Agg10merate enthalten. Sie erlaubten die ldentifikation folgender rnöglicher Quellen von fehlerhaften Messungen an Arbeitsplätzen mit erhöhter Luft-K0nzentrati0n von Nanopartikel Agglomeratenz - Ein Standard SMPS zeigte eine unglaubwürdige bimodale Partikelgrössenverteilung wenn er grössere Nan0par'til<e1Agg10merate gemessen hat. - Grosse Unterschiede im Bereich von Faktor tausend wurden festgestellt zwischen einem Diffusion Size Classiîier und einigen CPC (beziehungsweise dem SMPS). - Die Unterschiede zwischen CPC/SMPS und dem PAS waren geringer, aber abhängig von Grosse oder Typ des gemessenen Pulvers waren sie dennoch in der Grössenordnung von einer guten Grössenordnung. - Spezifische Schwierigkeiten und Unsicherheiten im Bereich von Arbeitsplatzmessungen wurden identitiziert: Hintergrundpartikel können mit Partikeln interagieren die während einem Arbeitsprozess freigesetzt werden. Solche Interaktionen erschweren eine korrekte Einbettung der Hintergrunds-Partikel-Konzentration in die Messdaten. - Elektromotoren produzieren grosse Mengen von Nanopartikeln und können so die Messung der prozessbezogenen Exposition stören. Fazit: Die Umfragen zeigten, dass Nanopartikel bereits Realitàt sind in der Schweizer Industrie und dass einige Unternehmen bereits grosse Mengen davon einsetzen. Die repräsentative Umfrage hat diese explosive Nachricht jedoch etwas moderiert, indem sie aufgezeigt hat, dass die Zahl der Unternehmen in der gesamtschweizerischen Industrie relativ gering ist. In den meisten Branchen (vor allem ausserhalb der Chemischen Industrie) wurden wenig oder keine Anwendungen gefunden, was schliessen last, dass die Einführung dieser neuen Technologie erst am Anfang einer Entwicklung steht. Auch wenn die Zahl der potentiell exponierten Arbeiter immer noch relativ gering ist, so unterstreicht die Studie dennoch die Notwendigkeit von Expositionsmessungen an diesen Arbeitsplätzen. Kenntnisse um die Exposition und das Wissen, wie solche Exposition korrekt zu messen, sind sehr wichtig, vor allem weil die möglichen Auswirkungen auf die Gesundheit noch nicht völlig verstanden sind. Die Evaluation einiger Geräte und Methoden zeigte jedoch, dass hier noch Nachholbedarf herrscht. Bevor grössere Mess-Studien durgefîihrt werden können, müssen die Geräte und Methodem für den Einsatz mit Nanopartikel-Agglomeraten validiert werden.

EAACI Position Paper: prevention of work-related respiratory allergies among pre-apprentices or apprentices and young workers.

ABSTRACT: Apprenticeship is a period of increased risk of developing work-related respiratory allergic diseases. There is a need for documents to provide appropriate professional advice to young adults aiming to reduce unsuitable job choices and prevent impairment from their careers. The present document is the result of a consensus reached by a panel of experts from European and non-European countries addressed to allergologists, pneumologists, occupational physicians, primary care physicians, and other specialists interested in this field, which aims to reduce work-related respiratory allergies (rhinoconjunctivitis and asthma) among allergic or nonallergic apprentices and other young adults entering the workforce. The main objective of the document is to issue consensus suggestions for good clinical practice based on existing scientific evidence and the expertise of a panel of physicians.

Bilateral uveal pigmented alterations with remarkable evolution: long term follow-up in a case of possible bilateral diffuse uveal melanocytic proliferation

Purpose: to describe a case of probable bilateral diffuse uveal melanocytic proliferation (BDUMP) with scleral involvement, free from systemic malignancies and cataract. Methods: fifty months of follow up with recurrent complete ophthalmological examinations, including fundus photography, fluorescein/indocyanine green angiography (FA) and optical coherence tomography (OCT). Investigations also included an electroretinography (ERG) and histological examination of scleral biopsy. Extraocular malignancies were repeatedly searched. Results: the patient was a 61 year-old Italian man with chronic hepatitis type C. At first visit his best corrected visual acuity (BCVA) was 20/32 in OS and 20/25 in OD. Funduscopy showed multiple patch-shaped pigmented alterations involving macular region and mid retinal periphery. FA showed corresponding areas of late-phase hyperfluorescent pinpoints (figure 1a, OS) and intemediate-phase hypocyanescence (figure 1b, OS), with subtle serous neurosensory retinal detachment confirmed by OCT. Photopic and scotopic ERG tested normal. Systemic prednisone was administered for one month without any improvement. After ten months round pigmentary lesions appeared also in superior scleral surface of both eyes. Biopsy allowed to disclose slightly pigmented spindle cells. BCVA worsened for further 10 months, with enlargement of FA alteration areas but lenses still clear. After 30 months spontaneous coalescence and atrophy of retinal lesions started, paralleled by progressive visual recovery. At the end of our follow up BCVA was 20/25 in OU while scleral pigmentary lesions remained unchanged. Conclusions: we report the case of a patient with main features of BDUMP and some unusual findings. Although not all classical diagnostic criteria were fulfilled, the presence of scleral pigmented lesions and spontaneous visual recovery may enlarge clinical spectrum of the disease.

Rôle des paramètres sociopolitiques et des connaissances dans la gestion des risques hydrologiques

Résumé Rôle des paramètres sociopolitiques et des connaissances dans la gestion des risques hydrologiques¦La recherche analyse (1) la mise en oeuvre de la gestion des risques hydrologiques et (2) les connaissances dont disposent les acteurs sur ces derniers, ainsi que (3) les interdépendances entre ces deux volets. Au total, trois études de cas ont été réalisées dont deux études régionales (ville de Berne, commune de Saillon) et une étude sur un acteur spécifique (les corporations de digues dans le canton de Berne). Les données empiriques ont été obtenues par des entretiens oraux semi-directifs et des enquêtes écrites.¦La gestion des risques hydrologiques est fortement influencée par des paramètres sociopolitiques, c'est-à-dire par les intérêts et les objectifs des acteurs, par les rapports de force entre ceux-ci ainsi que par les processus de négociation et de décision. Dans la pratique, les démarches de gestion se restreignent toutefois majoritairement aux aspects physiques, techniques et administratifs des risques hydrologiques. La dimension sociopolitique est ainsi négligée, ce qui est source de conflits qui ralentissent considérablement la planification de la protection contre les crues, voire la bloquent même complètement. La gestion des risques hydrologiques est en outre largement focalisée sur la réduction des aléas. Lés débats sur la vulnérabilité sont nettement plus rares bien qu'ils soient indispensables lorsqu'il s'agit de traiter les risques de façon holistique.¦Etant donné l'importance de la dimension sociopolitique et de la vulnérabilité, il est nécessaire que les démarches prévues dans la gestion des risques hydrologiques soient reconsidérées et adaptées. De plus, une meilleure intégration de tous les acteurs concernés est primordiale afin de trouver des solutions qui soient acceptables pour une majorité. Pour l'instant, le recours à des instruments de négociation est insuffisant.¦Les connaissances des risques hydrologiques et de leur gestion peuvent être classées en quatre répertoires (connaissances du système, de l'événement, de l'intervention et connaissances sociopolitiques) qui influent tous sur la réduction des risques. Parmi les facteurs les plus importants susceptibles de déclencher des transformations se trouvent l'occurrence de crues, la réalisation d'études (portant sur les aléas, la vulnérabilité, les mesures, etc.), l'échange de connaissances entre les acteurs, ainsi que la recherche de solutions lors de la gestion.¦Les caractéristiques des connaissances varient considérablement selon les acteurs. L'appartenance à un groupe donné ne permet toutefois pas à elle seule de déterminer l'état des connaissances : tous les acteurs peuvent avoir des connaissances pertinentes pour la gestion des risques. Les différences entre les acteurs rendent pourtant la communication compliquée. Ce problème pourrait être atténué par des médiateurs qui assureraient un travail de traduction. Dans la pratique, de telles instances manquent généralement.¦La gestion et les connaissances des risques hydrologiques sont fortement interdépendantes. L'état et les caractéristiques des connaissances déterminent directement la qualité de la protection contre les crues. Des lacunes ou des imprécisions peuvent donc entraîner une gestion non adaptée aux risques présents. Afin d'éviter une telle situation, il est important que les connaissances sur les risques hydrologiques et sur les possibilités d'y faire face soient régulièrement remises à jour. Ne devant pas se restreindre à l'expérience de crues passées, il est impératif qu'elles contiennent aussi des réflexions prospectives et des scénarios novateurs.¦La gestion n'est pas seulement demandeuse en connaissances, elle est également susceptible d'en générer de nouvelles et d'élargir les connaissances existantes. Il convient donc de considérer la création et le transfert de connaissances comme une tâche centrale de la gestion des risques.¦Zusammenfassung Die Rolle der soziopolitischen Parameter und des Wissens im Umgang mit hydrologischen Risiken¦Die Arbeit untersucht drei Themenbereiche: (1) den soziopolitischen Umgang mit hydrologischen Risiken, (2) das Wissen, über das die Akteure bezüglich der Hochwasserrisiken verfügen sowie (3) die Wechselwirkungen zwischen diesen beiden Themenfeldern. Insgesamt wurden drei Fallstudien durchgeführt, darunter zwei regionale Studien (Stadt Bern, Gemeinde Saillon) und eine Untersuchung eines spezifischen Akteurs (Schwellenkorporationen im Kanton Bern). Die empirischen Daten wurden anhand von halbstandardisierten Interviews und schriftlichen Umfragen erhoben.¦Das Management hydrologischer Risiken ist stark von soziopolitischen Parametern beeinflusst, d.h. von Interessen und Zielvorstellungen der Akteure, von Machtverhältnissen und von Verhandlungs- und Entscheidungsprozessen. Die in der Praxis vorgesehenen Schritte zur Reduktion der Hochwasserrisiken beschränken sich jedoch meist auf die physischen, administrativen und technischen Aspekte der Risiken. Die Vernachlässigung ihrer soziopolitischen Dimension führt zu Konflikten, welche die Planung von Hochwasserschutzprojekten deutlich verlangsamen oder gar blockieren. Des Weiteren konzentriert sich das Risikomanagement im Wesentlichen auf die Reduktion der Gefahren. Gesellschaftliche Debatten zur Vulnerabilität sind deutlich seltener, obschon sie für einen umfassenden Umgang mit Risiken unabdingbar sind.¦Angesichts der Bedeutung der soziopolitischen Dimension und der Vulnerabilität ist es notwendig, dass die Vorgehensweise im Risikomanagement überdacht und angepasst wird. Zudem ist eine bessere Integration aller betroffener Akteure unablässig, um mehrheitsfähige Lösungen zu finden. Zur Zeit ist der Rückgriff auf entsprechende Instrumente ungenügend.¦Das Wissen über hydrologische Risiken und deren Management kann in vier Repertoires eingeteilt werden (Systemwissen, Ereigniswissen, Interventionswissen, soziopolitisches Wissen), die alle bei der Reduktion von Risiken bedeutsam sind. Zu den wichtigsten Faktoren, die Wissenstransformationen auslösen, gehören Hochwasserereignisse, die Durchführung von Studien (zu Gefahren, zur Vulnerabilität, zu Massnahmen usw.), der Wissensaustausch zwischen Akteuren und die Suche nach Lösungen während des Risikomanagements.¦Die Merkmale der Wissensformen unterschieden sich stark zwischen den verschiedenen Akteuren. Die Zugehörigkeit eines Akteurs zu einer bestimmten Gruppe ist jedoch kein ausreichendes Kriterium, um dessen Wissensstand zu bestimmen: Alle Akteure können über Wissen verfügen, das für den Umgang mit Risiken relevant ist. Die Unterschiede zwischen den Akteuren gestalten die Kommunikation allerdings schwierig. Das Problem liesse sich entschärfen, indem Mediatoren eingesetzt würden, die als Übersetzer und Vermittler agierten. In der Praxis fehlen solche Instanzen weitgehend.¦Zwischen dem Umgang mit hydrologischen Risken und dem Wissen bestehen enge Wechselwirkungen. Der Zustand und die Eigenschaften der Wissensformen bestimmen direkt die Qualität des Hochwasserschutzes. Lückenhaftes und unpräzises Wissen kann demnach zu einem Risikomanagement führen, das den tatsächlichen Gegebenheiten nicht angepasst ist. Um eine solche Situation zu verhindern, muss das Wissen über Risiken und Hochwasserschutz regelmässig aktualisiert werden. Dabei darf es sich nicht auf die Erfahrung vergangener Hochwasser beschränken, sondern hat auch vorausschauende Überlegungen und neuartige Szenarien einzubeziehen.¦Das Risikomanagement benötigt nicht nur Wissen, es trägt auch dazu bei, neues Wissen zu t generieren und bestehendes zu erweitern. Die Erarbeitung und der Transfer von Wissen sind deshalb als zentrale Aufgaben des Risikomanagements zu betrachten.¦Abstract¦The role of socio-political parameters and of knowledge in the management of hydrological risks¦The purpose of the thesis is to analyse (1) the socio-political management of hydrological risks, (2) the knowledge about hydrological risks, and (3) the interaction between risk management and knowledge. Three case studies were carried out, two at a regional level (city of Berne, village of Saillon) and one about a specific stakeholder (the dyke corporations in the canton of Berne). Empirical data were collected by the means of semi-structured interviews and surveys.¦The management of hydrological risks is highly influenced by socio-political issues, i.e. by interests and goals of stakeholders, by the balance of power between stakeholders, as well as by negotiations and decision-making processes. In practice, however, risk management is mainly constrained by physical, technical, and administrative aspects. The neglect of the socio-political dimension may thus be the source of conflicts which significantly delay the planning and implementation of flood protection measures, or even stop them. Furthermore, risk management mostly concentrates on hazard reduction. Discussions on vulnerability issues are less frequent although they are fundamental for treating risks in a holistic manner.¦Because of the importance of the social-political dimension and of vulnerability issues, it is necessary that the common approach of managing hydrological risks is reconsidered and adapted. Moreover, the integration of all stakeholders that are concerned with hydrological risks is essential for finding solutions which are supported by a majority. For instance, the application of appropriate negotiation instruments is insufficient.¦Knowledge about hydrological risks and their management can be classified into four categories (system knowledge, event knowledge, intervention knowledge, socio-political knowledge) which are all influencing the reduction of risks. Among the most important factors that are likely to trigger knowledge transformations, one can point out flood events, studies about risk parameters (hazards, vulnerability, protection measures, etc.), knowledge exchange between stakeholders, and the search for solutions during risk management.¦The characteristics of knowledge vary considerably between stakeholders. The affiliation to a specific group is thus not a sufficient criterion to determine the quality of a stakeholder's knowledge: every stakeholder may have knowledge that is relevant for risk management. However, differences between stakeholders complicate the communication. This problem could be attenuated by mediators which ensure the translation between stakeholders. In practice, such instances are generally lacking.¦The management and knowledge of hydrological risks are highly interdependent. The state and the characteristics of the four categories of knowledge determine directly the quality of flood protection. Gaps and imprecison may thus lead to forms of management which are not adapted to the actual risks. This kind of situation can be avoided by updating regularly the knowledge about hydrological risks and about protection measures. However, knowledge must not be restricted to the experience of past floods. On the contrary, it is indispensable also to involve prospective reflections and new scenarios.¦Risk management does not only require knowledge, it may also generate new knowledge and enlarge existing knowledge. The creation and the transfer of knowledge has thus to be seen as a central task in risk management.

Valeur ajoutée de la supervision du médecin-assistant par un médecin de famille dans une permanence [Added value of family practitioners' supervision of junior doctors in a walk-in clinic].

The pending workforce crisis in family medicine has triggered various initiatives. This article describes the PMU-FLON walk-in clinic, a project of the Institute of General Medicine University of Lausanne. The working conditions in this clinic are close to that of a family practice. Doctors in training are supervised by family doctors who work part-time in the clinic. The objective is to improve training in the various fields of family medicine, from technical skills (improving optimal use of diagnostic tools), to integrating patients' requests in a more global patient-centered approach. This new educational model allows doctors in training to benefit from the specific approaches of different trainers. It will contribute to promoting quality family medicine in the future.

Introduction to the special issue on employment discrimination against immigrants

Purpose - This editorial aims to introduce the special issue on employment discrimination against immigrants. Design/methodology/approach - The first part is a commentary on key issues in the study of employment discrimination against immigrants. The second part presents the five articles in the special issue. Findings - The papers in this special issue focus on a variety of issues associated with employment discrimination against immigrants. For example, they consider: discrimination based on accents; differences among justice perceptions among immigrants and non-immigrants; the effects of negative stereotypes on workplace outcomes; the treatment of Hispanic immigrants; and the reasons for the lack of research on Hispanic immigrants. Research limitations/implications - The author comments on key issues that researchers of employment discrimination against immigrants have to take into account. These issues include: the appreciation of the diversity among immigrants; an understanding of the complexity of employment discrimination research; openness to cross-disciplinary approaches; and the consideration of employment discrimination within the context of the immigrant experience. The five articles that make up the special issues vary in their nature (empirical, critical), methodologies (quantitative, qualitative), locations (United States, Germany, and Canada), and implications. Practical implications - The issues discussed in the papers have important implications for understanding and overcoming employment discrimination against immigrants. Originality/value - The Journal of Managerial Psychology invited this special issue to initiate psychological research on employment discrimination against immigrants. The intent is to draw the attention of organizational scholars to the large, yet under-studied immigrant segment of the workforce.

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The chapter provides an account of the changing role played by active labour market policies (ALMPs) in Europe since the post-war years. Focusing on six countries (Sweden, Denmark, France, Germany, Italy, and the United Kingdom), it shows that the role of ALMPs is related to the broad economic situation. At times of rapid expansion and labour shortage, like the 1950s and 1960s, their key objective was to upskill the workforce. After the oil shocks of the 1970s, the raison d'être of ALMPs shifted from economic to social policy, and since the mid-1990s, we see the development of a new function, well captured by the notion of activation, which refers to the strengthening of work incentives and the removal of obstacles to employment, mostly for low-skilled people. The adequacy between economic context and policy is not always optimal, though. Like other ones, this policy domain suffers from inertia, with the result that the countries that have led the way in one period have more difficulty adapting to the economic conditions prevailing in the following one.

Situation et enjeux sanitaires aux Seychelles en 2012

Off the coast of Kenya, the Seychelles, home to 87,400 inhabitants mostly of African origin, have largely completed their demographic and epidemiologic transitions. Major investments in infrastructure and social services have fostered steady economic growth. Health care and education are free. The predominance of chronic non-communicable diseases and rapid aging of the population nonetheless present significant challenges for public health and the health system. Like the other small island states in the region, the Seychelles continue to be threatened by arbovirus outbreaks. Health indicators are good, but the geographic isolation, the small and aging population, and limited resources make a major challenge maintaining and sustaining an effective workforce of health professionals, a constantly evolving technical platform, and increasing amount of medications particularly in view of the increasing burden of chronic diseases.

Topics in public finance: social security and taxation

Summary The field of public finance focuses on the spending and taxing activities of governments and their influence on the allocation of resources and distribution of income. This work covers in three parts different topics related to public finance which are currently widely discussed in media and politics. The first two parts deal with issues on social security, which is in general one of the biggest spending shares of governments. The third part looks at the main income source of governments by analyzing the perceived value of tax competition. Part one deals with the current problem of increased early retirement by focusing on Switzerland as a special case. Early retirement is predominantly considered to be the result of incentives set by social security and the tax system. But the Swiss example demonstrates that the incidence of early retirement has dramatically increased even in the absence of institutional changes. We argue that the wealth effect also plays an important role in the retirement decision for middle and high income earners. An actuarially fair, but mandatory funded system with a relatively high replacement rate may thus contribute to a low labor market participation rate of elderly workers. We provide evidence using a unique dataset on individual retirement decisions in Swiss pension funds, allowing us to perfectly control for pension scheme details. Our findings suggest that affordability is a key determinant in the retirement decisions. The higher the accumulated pension capital, the earlier men, and to a smaller extent women, tend to leave the workforce. The fact that early retirement has become much more prevalent in the last 15 years is a further indicator of the importance of a wealth effect, as the maturing of the Swiss mandatory funded pension system over that period has led to an increase in the effective replacement rates for middle and high income earners. Part two covers the theoretical side of social security. Theories analyzing optimal social security benefits provide important qualitative results, by mainly using one general type of an economy. Economies are however very diverse concerning numerous aspects, one of the most important being the wealth level. This can lead to significant quantitative benefit differences that imply differences in replacement rates and levels of labor supply. We focus on several aspects related to this fact. In a within cohort social security model, we introduce disability insurance with an imperfect screening mechanism. We then vary the wealth level of the model economy and analyze how the optimal social security benefit structure or equivalently, the optimal replacement rates, changes depending on the wealth level of the economy, and if the introduction of disability insurance into a social security system is preferable for all economies. Second, the screening mechanism of disability insurance and the threshold level at which people are defined as disabled can differ. For economies with different wealth levels, we determine for different thresholds the screening level that maximizes social welfare. Finally, part three turns to the income of governments, by adding an element to the controversy on tax competition versus tax harmonization.2 Inter-jurisdictional tax competition can generate at least two potential benefits or costs: On a public level, tax competition may result in a lower or higher efficiency in the production of public services. But there is also a more private benefit in the form of an option for individuals to move to a community with a lower tax rate in the future. To explore the value citizens attach to tax competition we analyze a unique popular vote for a complete tax harmonization between communities in the third largest Swiss canton, Vaud. Although a majority of voters would have seemingly benefited from replacing the current tax rate by a revenue-neutral average tax rate, the proposal was rejected by a large margin. Our estimates suggest that the estimated combined perceived benefit from tax competition is in the range of 10%.

Integrating receptor interactions and dynamics and Interference with endocrine disruptors in the mechanisms of action of PPAR nuclear receptors

Abstract Peroxisome Proliferator-Activated Receptors (PPARs) form a family of three nuclear receptors regulating important cellular and metabolic functions. PPARs control gene expression by directly binding to target promoters as heterodimers with the Retinoid X Receptor (RXR), and their transcriptional activity is enhanced upon activation by natural or pharmacological ligands. The binding of PPAR/RXR heterodimers on target promoters allows the anchoring of a series of coactivators and corepressors involved in promoter remodeling and the recruitment of the transcription machinery. The transcriptional output finally depends on a complex interplay between (i) the respective expression levels of PPARs, RXRs and of other nuclear receptors competing for DNA binding and RXR recruitment, (ii) the availability and the nature of PPAR and RXR ligands, (iii) the expression levels and the nature of the different coactivators and corepressors and (iv) the sequence and the epigenetic status of the promoter. Understanding how all these factors and signals integrate and fine-tune transcription remains a challenge but is necessary to understand the specificity of the physiological functions regulated by PPARs. The work presented herein focuses on the molecular mechanisms of PPAR action and aims at understanding how the interactions and mobility of the receptor modulate transcription in the physiological context of a living cell: Such observations in vivo rely on the use of engineered fluorescent protein chimeras and require the development and the application of complementary imaging techniques such as Fluorescence Recovery After Photobleaching (FRAP), Fluorescence Resonance Energy Transfer (FRET) and Fluorescence Correlation Spectroscopy (FCS). Using such techniques, PPARs are shown to reside solely in the nucleus where they are constitutively associated with RXR but transcriptional activation by ligand binding -does not promote the formation of sub-nuclear structures as observed with other nuclear receptors. In addition, the engagement of unliganded PPARs in large complexes of cofactors in living cells provides a molecular basis for their ligand-independent activity. Ligand binding reduces receptor diffusion by promoting the recruitment of coactivators which further enlarge the size of PPAR complexes to acquire full transcriptional competence. Using these molecular approaches, we deciphered the molecular mechanisms through which phthalates, a class of pollutants from the plastic industry, interfere with PPARγ signaling. Mono-ethyl-hexyl-phthalate (MEHP) binding induces the recruitment of a specific subset of cofactors and translates into the expression of a specific subset of target genes, the transcriptional output being strongly conditioned by the differentiation status of the cell. This selective PPARγ modulation induces limited adipogenic effects in cellular models while exposure to phthalates in animal models leads to protective effects on glucose tolerance and diet-induced obesity. These results demonstrate that phthalates influence lipid and carbohydrate metabolism through complex mechanisms which most likely involve PPARγ but also probably PPARα and PPARß, Altogether, the molecular and physiological demonstration of the interference of pollutants with PPAR action outlines an important role of chemical exposure in metabolic regulations. Résumé Les PPARs (Peroxisome Proliferator-Activated Receptors) forment une famille de récepteurs nucléaires qui régulent des fonctions cellulaires et métaboliques importantes. Les PPARs contrôlent l'expression des gènes en se liant directement à leurs promoteurs sous forme d'hétérodimères avec les récepteurs RXR (Retinoid X Receptor), et leur activité transcriptionnelle est stimulée par la liaison de ligands naturels ou pharmacologiques. L'association des hétérodimères PPAR/RXR avec les promoteurs des gènes cibles permet le recrutement de coactivateurs et de corépresseurs qui vont permettre le remodelage de la chromatine et le recrutement de la machinerie transcriptionnelle. Les actions transcriptionnelles du récepteur dépendent toutefois d'interactions complexes qui sont régulées par (i) le niveau d'expression des PPARs, des RXRs et d'autres récepteurs nucléaires entrant en compétition pour la liaison à l'ADN et l'association avec RXR, (ii) la disponibilité et la nature de ligands de PPAR et de RXR, (iii) les niveaux d'expression et la nature des différents coactivateurs et corépresseurs et (iv) la séquence et le marquage épigénétique des promoteurs. La compréhension des mécanismes qui permettent d'intégrer ces aspects pour assurer une régulation fine de l'activité transcriptionnelle est un défi qu'il est nécessaire de relever pour comprendre la spécificité des fonctions physiologiques régulées par les PPARs. Ce travail concerne l'étude des mécanismes d'action moléculaire des PPARs et vise à mieux comprendre comment les interactions du récepteur avec d'autres protéines ainsi que la mobilité de ce dernier régulent son activité transcriptionnelle dans le contexte physiologique des cellules vivantes. De telles observations reposent sur l'emploi de protéines fusionnées à des protéines fluorescentes ainsi que sur le développement et l'utilisation de techniques d'imagerie complémentaires telles que le FRAP (Fluorescence Recovery After Photobleaching), le FRET (Fluorescence Resonance Energy Transfer) ou la FCS (Fluorescence Corrélation Spectroscopy). En appliquant ces méthodes, nous avons pu montrer que les PPARs résident toujours dans le noyau où ils sont associés de manière constitutive à RXR, mais que l'ajout de ligand n'induit pas la formation de structures sub-nucléaires comme cela a pu être décrit pour d'autres récepteurs nucléaires. De plus, les PPARs sont engagés dans de larges complexes protéiques de cofacteurs en absence de ligand, ce qui procure une explication moléculaire à leur activité ligand-indépendante. La liaison du ligand réduit la vitesse de diffusion du récepteur en induisant le recrutement de coactivateurs qui augmente encore plus la taille des complexes afin d'acquérir un potentiel d'activation maximal. En utilisant ces approches moléculaires, nous avons pu caractériser les mécanismes permettant aux phtalates, une classe de polluants provenant de l'industrie plastique, d'interférer avec PPARγ. La liaison du mono-ethyl-hexyl-phtalate (NERF) à PPARγ induit un recrutement sélectif de cofacteurs, se traduisant par l'induction spécifique d'un sous-ensemble de gènes qui varie en fonction du niveau de différentiation cellulaire. La modulation sélective de PPARγ par le MEHP provoque une adipogenèse modérée dans des modèles cellulaires alors que l'exposition de modèles animaux aux phtalates induit des effets bénéfiques sur la tolérance au glucose et sur le développement de l'obésité. Toutefois, les phtalates ont une action complexe sur le métabolisme glucido-lipidique en faisant intervenir PPARγ mais aussi probablement PPARα et PPARß. Cette démonstration moléculaire et physiologique de l'interférence des polluants avec les récepteurs nucléaires PPAR souligne un rôle important de l'exposition à de tels composés dans les régulations métaboliques.

The positive effects of a protean career attitude for self-initiated expatriates: Cultural adjustment as a mediator

Purpose - The authors sought to explain why and how protean career attitude might influence self-initiated expatriates' (SIEs) experiences positively. A mediation model of cultural adjustment was proposed and empirically evaluated. Design/methodology/approach - Data from 132 SIEs in Germany containing measures of protean career attitude, cultural adjustment, career satisfaction, life satisfaction, and intention to stay in the host country were analysed using path analysis with a bootstrap method. Findings - Empirical results provide support for the authors' proposed model: the positive relations between protean career attitude and the three expatriation outcomes (career satisfaction, life satisfaction and intention to stay in the host country) were mediated by positive cross-cultural adjustment of SIEs. Research limitations/implications - All data were cross-sectional from a single source. The sample size was small and included a large portion of Chinese participants. The study should be replicated with samples in other destination countries, and longitudinal research is suggested. Practical implications - By fostering both a protean career attitude in skilled SIE employees and their cultural adjustment, corporations and receiving countries could be able to retain this international workforce better in times of talent shortage. Originality/value - This study contributes to the scarce research on the conceptual relatedness of protean career attitude and SIEs, as well as to acknowledging the cultural diversity of the SIE population.

The pressure cooker technique for the treatment of brain AVMs.

Arteriovenous malformations (AVMs) may be cured by injecting liquid embolic agents such as Onyx. Reflux, however, can sometimes be difficult to control and may jeopardize a complete embolization. The pressure cooker technique (PCT) was designed to create an anti-reflux plug by trapping the detachable part of an Onyx-compatible microcatheter with coils and glue in order to obtain wedge-flow conditions, thereby enabling a better understanding of macrofistulous AVMs and a more comprehensive, forceful and controlled Onyx embolization. The PCT might enlarge the range of AVMs amenable to endovascular cure. Three illustrative cases are presented.

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In so-called unisexual teleost fishes, a broad spectrum of evolutionaty stages with varying amounts of sexual elements has evolved. These range from pure sperm-dependent parthenogenesis (gynogenesis) without or with different amounts of paternal leakage to hybridogenesis with hemiclonal diploid gametogenesis or genome elimination folowed by meiosis (meiotic hybridogenesis). All of these phenomena are hybrid origin. Many of these fish form complexes which involve the coexistence of one or more sexually reproducing species with derived all-female forms that have various ploidy levels and reproductive modes, including gynogenesis, (meiotic) hybridogenesis nnd sexual reproduction. In teleosts, parthenogenetic reproduction is strictly dependent on sperm to initate embryonic development. As opposed to true parthenogenesis, sperm-dependent parthenogenetic teleost lineages must primarily coexist with their "sperm donor", usually males from a parental sexual lineage or from a related sexual species. In some systems, gynogens were able to escape from their initial sperm donors ("host switch") and therefore, to enlarge their ranges and ecological niches. Sperm donors normally do not contribue genetically to the next generation. However, paternal leakage is observed in many systems contributing differing amounts of genetic material (from microchromosomes to entire chromosome sets) allowing interaction between genomes of different origin. Hybridogenesis is similar to gynogenesis in depending upon coexisence with sexual species but incorporates recombined genetic material by true fertilizazion. While hybridogens usually form clonal gametes, some triploids are capable of genome elimination followed by a normal diploid meiosis. Sperm-dependent parthenogenesis and hybridogenesis combine disadvantages and advantages from both sexuality and asexuality. Here, we give an overview of sperm-dependent breeding complexes in fishes, discuss the evolutionary consequences of paternal leakage, and speculate about the evolutionary significance of intergenomic (re)combination.